crossing96/oncoscreening huggingface dataset:
Erdafitinib in the Treatment of Metastatic Urothelial Carcinoma.	A Hispanic man, aged 42 years, was diagnosed with stage IV metastatic urothelial bladder cancer (MUBC) with nonregional lymphadenopathies and lung, bone, and skin involvement. He received first-line treatment with gemcitabine and cisplatin for 6 cycles, achieving a partial response (PR). Next, he received immunotherapy maintenance with avelumab for 4 months until disease progression. A next-generation sequencing test of paraffin-embedded tumor tissue identified a fibroblast growth factor receptor 3 (FGFR3) S249C missense mutation.	bladder
Atypical Recurrent Renal Cell Carcinoma of the Ipsilateral Ureter Showing Typical Symptoms of Upper Urinary Tract Urothelial Carcinoma: A Case Report and Literature Review.	"BACKGROUND: Ureteral metastasis is a rare phenomenon. Synchronous recurrence in both the pelvis and ureter with symptoms that are typical of upper urinary tract urothelial carcinoma (UTUC) has not been reported previously. METHODS: We present a case of metastasis of clear cell renal cell carcinoma (ccRCC) to the ipsilateral pelvis and ureter in a 37-year-old man who underwent open partial nephrectomy (PN) after laparoscopic exploration 20 months after surgery. We suspected painless hematuria with clots and upper UTUC based on the imagological diagnosis. We performed complete transperitoneal laparoscopic nephroureterectomy in a single position. We also searched PubMed for studies with the keywords ""renal cell carcinoma"" and ""ureteral metastasis"" that had been published since 2000. RESULTS: Postoperative pathology demonstrated ccRCC in the left pelvis that had spread along the ureter. The patient was discharged 1 week after surgery, without a drainage tube, and free to eat and perform normal activities. We identified 10 cases from nine studies that had been published since 2000. Nephrectomy was performed in all 10 cases, and nine of the patients had hematuria. Open ureterectomy was performed on two patients who had ipsilateral ureteral metastasis. CONCLUSIONS: Recurrent ccRCC in the ureter is rare. Due to the difficulty in distinguishing it from ipsilateral upper UTUC, complete transperitoneal laparoscopic nephroureterectomy in a single position is a safe and feasible treatment option in this situation."	bladder
Safety and effectiveness of pembrolizumab monotherapy in Japanese patients with unresectable urothelial carcinoma: a nation-wide post-marketing surveillance.	BACKGROUND: This study was conducted to identify factors associated with the safety and effectiveness of pembrolizumab in Japanese patients with unresectable urothelial carcinoma and to confirm the real-world safety and effectiveness of pembrolizumab in Japanese patients. METHODS: This multicenter, observational, post-marketing surveillance was conducted over a 1-year observation period starting at pembrolizumab initiation (200-mg pembrolizumab every 3 weeks); data were collected from case report forms (3 months and 1 year). Safety measures included treatment-related adverse events and adverse events of special interest (AEOSI). Effectiveness assessments included tumor response, objective response rate (ORR), and disease control rate (DCR). RESULTS: Overall, 1293 patients were evaluated for safety and 1136 for effectiveness. At 12 months, the treatment-related adverse event incidence was 53.8% (n = 696) and that of AEOSI was 25.0% (n = 323). The most frequent AEOSI of any grade were endocrinological disorder (10.4%, n = 134), interstitial lung disease (ILD) (7.2%, n = 93), and hepatic function disorder (4.9%, n = 64). Multivariate analysis demonstrated that the risk of developing ILD was almost seven times greater (odds ratio 6.60) in patients with a comorbidity of ILD, and approximately twice as high in patients aged ≥ 65 years (odds ratio 2.24) and with smoking history (odds ratio 1.79). The ORR was 26.1% and the DCR was 50.7%. The ORR was 46.4% in patients with a Bellmunt risk score of 0 and decreased as the Bellmunt risk score increased. CONCLUSIONS: This post-marketing surveillance confirmed the safety and effectiveness of pembrolizumab in Japanese patients with unresectable urothelial carcinoma in the real-world setting.	bladder
Comet-FISH analysis of urothelial cells. A screening opportunity for bladder cancer?	INTRODUCTION: Bladder cancer (BCa) is the most frequent cancer of the urinary tract, with more than 500,000 reported cases and nearly 200,000 related deaths yearly. Cystoscopy is the standard examination used for the initial diagnosis and follow-up of BCa in the noninvasive stage. However, the American Cancer Society does not include BCa screening in its list of recommended cancer screenings. AREAS COVERED: Recently, several urine-based bladder tumor markers (UBBTMs) that identify genomic, transcriptomic, epigenetic, or protein alterations have been introduced, some of which have been approved by the Food and Drug Administration (FDA) to improve its diagnosis and surveillance. Several biomarkers have been found in the tissues and blood of individuals with BCa or predisposed to develop the disease, further enriching our information. EXPERT OPINION: From a prevention perspective, alkaline Comet-FISH could be a valuable tool with broad potential for clinical application. Furthermore, a comet assay could be more beneficial for diagnosing and monitoring bladder cancer and determining individual susceptibility. Thus, we recommend further studies to understand the potential of this combined assay in the general population as a potential screening test and in patients initiated into the diagnostic process.	bladder
Competition between p53 and YY1 determines PHGDH expression and malignancy in bladder cancer.	PURPOSE: Serine metabolism is frequently dysregulated in many types of cancers and the tumor suppressor p53 is recently emerging as a key regulator of serine metabolism. However, the detailed mechanism remains unknown. Here, we investigate the role and underlying mechanisms of how p53 regulates the serine synthesis pathway (SSP) in bladder cancer (BLCA). METHODS: Two BLCA cell lines RT-4 (WT p53) and RT-112 (p53 R248Q) were manipulated by applying CRISPR/Cas9 to examine metabolic differences under WT and mutant p53 status. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and non-targeted metabolomics analysis were adopted to identify metabolomes changes between WT and p53 mutant BLCA cells. Bioinformatics analysis using the cancer genome atlas and Gene Expression Omnibus datasets and immunohistochemistry (IHC) staining was used to investigate PHGDH expression. Loss-of-function of PHGDH and subcutaneous xenograft model was adopted to investigate the function of PHGDH in mice BLCA. Chromatin immunoprecipitation (Ch-IP) assay was performed to analyze the relationships between YY1, p53, SIRT1 and PHGDH expression. RESULTS: SSP is one of the most prominent dysregulated metabolic pathways by comparing the metabolomes changes between wild-type (WT) p53 and mutant p53 of BLCA cells. TP53 gene mutation shows a positive correlation with PHGDH expression in TCGA-BLCA database. PHGDH depletion disturbs the reactive oxygen species homeostasis and attenuates the xenograft growth in the mouse model. Further, we demonstrate WT p53 inhibits PHGDH expression by recruiting SIRT1 to the PHGDH promoter. Interestingly, the DNA binding motifs of YY1 and p53 in the PHGDH promoter are partially overlapped which causes competition between the two transcription factors. This competitive regulation of PHGDH is functionally linked to the xenograft growth in mice. CONCLUSION: YY1 drives PHGDH expression in the context of mutant p53 and promotes bladder tumorigenesis, which preliminarily explains the relationship between high-frequency mutations of p53 and dysfunctional serine metabolism in bladder cancer.	bladder
Genital Sparing Robot-Assisted Radical Cystectomy with Intracorporeal Neobladder & Paravaginal Repair.	"OBJECTIVE: Vaginal prolapse is a known complication after radical cystectomy, requiring additional procedures in 10% of the patients.(1) This results from loss of level I and II vaginal support due to the removal of pelvic structures. In addition, a neobladder urinary diversion, with Valsalva voiding, predisposes to vaginal prolapse. A genital-sparing approach with paravaginal repair can help prevent such complications. METHODS: The genital sparing technique preserves the uterus, fallopian tubes, ovaries, and vagina, while paravaginal repair involves suturing of the lateral vaginal wall to the arcuate fascia located on the medial aspect of the obturator internus muscle. The procedure begins by placing the patient in a lithotomy position, with a steep Trendelenburg. Standard 6 port cystectomy configuration is utilized with an additional 15 mm port for bowel anastomosis. Initially, the ureters and lateral bladder space are mobilized. Posteriorly a dissection plane is developed separating the bladder from the anterior vaginal wall. Distal dissection is carefully performed in that plane to avoid disrupting the urethral-external sphincter complex. Then the bladder is dropped from anterior attachments, the Dorsal venous complex (DVC) and bladder neck are exposed. Urethra is transected distal to the bladder neck, after circumferential mobilization, to complete the cystectomy, again avoiding disruption of the continence mechanism, and opening the endo-pelvic fascia. Cystectomy and pelvic lymph node dissection are completed in a standard fashion. The arcuate fascia is identified bilaterally for level I paravaginal repair. The lateral aspect of the paravaginal tissue is secured to this ligament, using 3 interrupted Polydioxanone (PDS) sutures, bilaterally. An ileal ""Hautman's W pouch"" neobladder is constructed using 50 cm of the small intestine, similar to the previously reported technique.(2) Bricker-type uretero-ileal anastomosis is performed over a double J stent. Bowel continuity is restored by a side-to-side anastomosis using endo-GIA (gastrointestinal anastamosis EndoGIA(TM) ) staplers. RESULTS: No intra or postoperative complications were noted. Robot dock time was 8 hours and 23 minutes with an EBL of 100 mL. The patient was discharged on post operative day (POD) 6 and Foley catheter with ureteral stents was removed on POD 27 after a cystogram confirmed no leaks. At 6-month follow-up, the patient reported good continence using a single pad, voiding every 3-4 hours. Fluoro-urodynamics demonstrated 651 mL capacity, low-pressure voiding, minimal residual urine, and no reflux. No prolapse was noted on fluoroscopy and pelvic examination with the Valsalva maneuver. The patient reported a good satisfaction level, regarding her urinary symptoms. CONCLUSION: We report satisfactory short-term outcomes of a feasible technique to prevent postcystectomy prolapse; however, long-term follow-up of a larger cohort can help establish its efficacy."	bladder
Bladder perforation as a complication of transurethral resection of bladder tumors: the predictors, management, and its impact in a series of 1570 at a tertiary urology institute.	OBJECTIVES: To report the incidence, predictors, the impact of bladder perforation (BP), and our protocol of management in patients who underwent trans-urethral resection of bladder tumor (TURBT). METHODS: This is a retrospective study, between 2006 and 2020, on patients who underwent TURBT for non-muscle-invasive bladder cancer (NMIBC). Bladder perforation was defined as any full thickness resection of the bladder wall. Bladder perforations were managed based on their severity and type. Small BP with no or mild symptoms were managed with prolongation of urethral catheters. Those with significant extraperitoneal extravasations were managed by insertion of a tube drain (TD). Abdominal exploration was done for extensive BP and all intraperitoneal extravasations. RESULTS: Our study included 1,570 patients, the mean age was 58 ± 11 years and 86% were males. Bladder perforation was recorded in 10% (n = 158) of the patients. The perforation was extraperitoneal in 95%, and in 86%, the perforation was associated with no symptoms, mild symptoms, or mild fluid extravasation that required only prolongation of the urethral catheter. On the other hand, active intervention was required for the 21 remaining patients (14%) with TD being the most frequent management. History of previous TURBT (p = 0.001) and obturator jerk (p = 0.0001) were the only predictors for BP. CONCLUSIONS: The overall incidence of bladder perforation is 10%; however, 86% required only prolongation of urethral catheter. Bladder perforation did not affect the probability for tumor recurrence, tumor progression nor radical cystectomy.	bladder
Impact of a novel immune and nutritional score on prognosis in patients with upper urinary tract urothelial carcinoma following radical nephroureterectomy.	BACKGROUND: This study aimed to evaluate the clinical significance of a novel immune and nutritional score combining prognostic values of the controlling nutritional status (CONUT) score and prognostic immune and nutritional index (PINI) on long-term outcomes in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). METHODS: This study analyzed 437 consecutive patients with UTUC treated by RNU. Restricted cubic splines were used to visualize the relation of PINI with Survival in patients with UTUC. The PINI was stratified into low- (1) and high-PINI (0) categories. The CONUT score was divided into three groups: Normal (1), Light (2), and Moderate/severe (3). Subsequently, patients were grouped according to CONUT-PINI score (CPS) (CPS group 1; CPS group 2; CPS group 3; and CPS group 4). Survival curves were plotted using the Kaplan-Meier method and log-rank test. The Cox proportional hazards regression model was used to determine the risk factors associated with overall Survival (OS) and cancer-specific Survival (CSS). By comprising independent prognostic factors, a predictive nomogram was constructed. RESULTS: PINI and CONUT score were identified as independent prognostic factors for OS and CSS. Kaplan-Meier survival analysis showed that the high CPS group was associated with worse OS and CSS than the low CPS group. Multivariate Cox regression and competing risk analyses showed that CPS, LVI, T stage, margin, and pN were independent factors associated with OS and CSS. Based on these five significant factors, we constructed a prognostic model for predicting clinical outcomes. The receiver operating characteristic curve indicated that the model had excellent predictive abilities for survival. The C-index of this model for OS and CSS were 0.773, and 0.789, respectively. The nomogram for OS and CSS showed good discrimination and calibration. Decision curve analysis (DCA) showed that this nomogram has a higher net benefit. CONCLUSION: The CPS combined the prognostic capacity of PINI and CONUT score and was able to predict patient outcomes in our cohort of UTUC patients. We have developed a nomogram to facilitate the clinical use of the CPS and provide accurate estimates of survival for individuals.	bladder
The poor antitumor effect of pembrolizumab in advanced upper urothelial carcinoma with renal parenchymal invasion.	OBJECTIVES: We investigated poor prognosticators in advanced or unresectable urothelial carcinoma, focusing on renal parenchymal invasion (RPI). METHODS: This study included 48 bladder cancer (BC) and 67 upper tract urothelial carcinoma (UTUC) patients treated with pembrolizumab from December 2017 to September 2022 at Kobe University Hospital. Medical records were retrospectively reviewed for clinical characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Multivariate analyses were performed using the Cox proportional hazard regression model to identify parameters associated with either PFS or OS. RESULTS: Of 67 UTUC patients, 23 had RPI and 41 patients did not, while 3 cases could not be evaluated. Patients with RPI were predominantly elderly and had liver metastases. ORR for patients with RPI was 8.7%, while it was 19.5% for those without RPI. PFS was significantly shorter for patients with RPI compared with those without RPI. Patients with RPI had significantly shorter OS than those without RPI. On multivariate analysis, performance status (PS) ≥ 2, neutrophil-lymphocyte ratio (NLR) ≥ 3, C-reactive protein ≥0.3 mg/dL and RPI were independent prognostic factors for PFS. PS ≥ 2, NLR ≥ 3, visceral metastasis and RPI were independent prognostic factors for OS. UTUC patient OS was significantly shorter than BC patient OS, while no significant difference in PFS or OS was observed between BC patients and UTUC patients without RPI. CONCLUSIONS: RPI was a poor prognostic factor in advanced urothelial carcinoma treated with pembrolizumab, possibly resulting in a poorer prognosis for UTUC compared with BC.	bladder
SCARA5 as a downstream factor of PCAT29, inhibits proliferation, migration, and invasion of bladder cancer.	Scavenger receptor class A, member 5 (SCARA5) has been identified a novel tumor suppressor in several cancers. However, the functional and underlying mechanism of SCARA5 in bladder cancer (BC) need investigation. Here, we found SCARA5 expression was downregulated in both BC tissues and cell lines. Low SCARA5 in BC tissues was associated with a shorter overall survival. Moreover, SCARA5 overexpression reduced BC cell viability, colony formation, invasion, and migration. Further investigation demonstrated that the expression of SCARA5 was negatively regulated by miR-141. Furthermore, the long non-coding RNA prostate cancer associated transcript 29 (PCAT29) inhibited the proliferation, invasion, and migration of BC cells by sponging miR-141. Luciferase activity assays revealed that PCAT29 targeted miR-141 and miR-141 targeted SCARA5. In conclusion, SCARA5, as a downstream factor of the PCAT29/miR-141 axis, inhibited the proliferation, migration, and invasion of BC cells. These findings provide novel insights into the detailed molecular mechanisms of BC development.	bladder
Stage-dependent survival in patients treated with neoadjuvant chemotherapy and radical cystectomy.	BACKGROUND: The aim of this study is to investigate the differential stage-dependent outcomes of patients undergoing radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). METHODS: We performed a retrospective analysis of 1422 patients with cT2-4N0 MIBC treated with RC, with/without cisplatin-based NAC, from our multicenter cooperation program (treated period: 1992-2021). Patients were stratified according to their pathologic stage at RC. Cancer-specific survival (CSS) and overall survival (OS) were calculated using mixed-effects Cox analysis. RESULTS: Analysis was conducted on 761 patients treated with NAC followed by RC and 661 treated with RC only (median follow-up 19 months). Of 337 (24%) patients who died, 259 (18%) died of bladder cancer. On univariable analyses, increased pathologic stage was significantly associated with worse CSS (HR=1.59, 95% CI 1.46-1.73; P<0.01) and OS (HR=1.58, 95% CI 1.47-1.71; P<0.001). On multivariable mixed-effects model, patients after RC only had significantly worse CSS with stage pT≥3/N1-3 and OS with stage pT≥2/N0-3 compared to those with stage pT≤1N0. Patients after RC and NAC had significantly worse CSS and OS already at stage ypT≥2/N0-3 compared to those with ypT≤1N0. On subgroup analyses, CSS (HR=4.26; 95% CI 2.03-8.95; P<0.001) but not OS (HR=1.1; 95% CI 0.5-2.4; P=0.81) was worse for pT2N0 patients after NAC versus no-NAC. This difference was not maintained on multivariable analysis. CONCLUSIONS: NAC improves pathologic stage at the time of RC. Patients with residual MIBC after NAC have worse survival outcomes compared to those with the same pathologic stage who did not receive NAC, suggesting a need for better adjuvant therapy in these patients.	bladder
Cutaneous metastasis in bladder cancer.	Cutaneous manifestation of cancers is a rare occurrence, even more so for bladder cancer, with a limited number of published reports. Iatrogenic implantation has been a major cause for it. With no clear distinction pattern from other common dermatological lesions, scattered occurrence, and poor survival; no definitive strategies are present for the management of these dermal manifestations. The present article describes a case of scalp lesion consistent with metastatic urothelial carcinoma along with a review of the literature.	bladder
[A Case of Refractory Lymphatic Leakage after Robot-Assisted Radical Cystectomy].	A 78-year-old male visited the referring hospital because of asymptomatic gross hematuria. The patient was diagnosed with bladder cancer, clinical stage T3aN2M0, after multiple tumors were found in the bladder by cystoscopy and bilateral obturator lymph node metastases were found by contrast-enhanced thoracoabdominal-pelvic computed tomography. After neoadjuvant chemotherapy, the patient underwent robot-assisted radical cystectomy and pelvic lymph node dissection, followed by bilateral ureterocutaneostomy for urinary diversion. Postoperatively, the drainage volume from the pelvic drain ranged from 1,000 to 3,000 ml/day. We suspected lymphatic leakage based on the results of biochemical tests of the drainage fluid. Lymphangiography was conducted to confirm the diagnosis of lymphatic leakage, and lymphatic embolization was performed simultaneously. The patient underwent lymphangiography four times, but the lymphatic leakage persisted. Surgical treatment was considered, and lymphangioscintigraphy was conducted to search for areas of lymphatic leakage that could not be delineated by lymphangiography. Ascites decreased significantly after lymphangioscintigraphy.	bladder
Establishment of a prognostic model to predict chemotherapy response and identification of RAC3 as a chemotherapeutic target in bladder cancer.	"Cisplatin-based chemotherapy is considered the primary treatment option for patients with advanced bladder cancer (BCa). However, the objective response rate to chemotherapy is often unsatisfactory, leading to a poor 5-year survival rate. Furthermore, current strategies for evaluating chemotherapy response and prognosis are limited and inefficient. In this study, we aimed to address these challenges by establishing a chemotherapy response type gene (CRTG) signature consisting of 9 genes and verified the prognostic value of this signature using TCGA and GEO BCa cohorts. The risk scores based on the CRTG signature were found to be associated with advanced clinicopathological status and demonstrated favorable predictive power for chemotherapy response in the TCGA cohort. Meanwhile, tumors with high risk scores exhibited a tendency toward a ""cold tumor"" phenotype. These tumors showed a low abundance of T cells, CD8+ T cells and cytotoxic lymphocytes, along with a high abundance of cancer-associated fibroblasts. Moreover, they displayed higher mRNA levels of these immune checkpoints: CD200, CD276, CD44, NRP1, PDCD1LG2 (PD-L2), and TNFSF9. Furthermore, we developed a nomogram that integrated the CRTG signature with clinicopathologic risk factors. This nomogram proved to be a more effective tool for predicting the prognosis of BCa patients. Additionally, we identified Rac family small GTPase 3 (RAC3) as a biomarker in our model. RAC3 was found to be overexpressed in chemoresistant BCa tissues and enhance the chemotherapeutic resistance of BCa cells in vitro and in vivo by regulating the PAK1-ERK1/2 pathway. In conclusion, our study presents a novel CRTG model for predicting chemotherapy response and prognosis in BCa. We also highlight the potential of combining chemotherapy with immunotherapy as a promising strategy for chemoresistant BCa and that RAC3 might be a latent target for therapeutic intervention."	bladder